Animal tumorigenesis models with unique qualitative or quantitative sensitivity to chemical carcinogens are utilized to study mechanisms and modifying factors in carcinogenesis. In a project employing athymic nude mice, transplacental or intraperitoneal exposure of nudes to the direct-acting carcinogen ethylnitrosourea (ENU) caused the appearance of skin tumors (sebaceous adenomas and papillomas), with an incidence ten times greater than that of the nu/+ littermates. An investigation of the reason for this difference is in progress and includes topical treatment of nu/nu and nu/+ mice with carcinogens and uv light, thymectomy of nu/+ newborns and thymus transplants to nu/nu animals. Strain A mice have high quantitative sensitivity to the induction of lung tumors by carcinogens and have been used as a model for assessing the effects of very low doses of the environmental carcinogen, dimethylnitrosamine (DMN). After 16 weeks of exposure to 500 ppb DMN, 44 per cent of the males had a lung tumor, compared with 8 per cent of controls. Even at 10 ppb DMN, 20 per cent of the males were tumor-bearing. This model is now being improved by systematic investigation of effect of diet and of exposure time, and will then be used for a large dose-response study. Determination of the effects of concurrent administration of ethanol, which inhibits liver metabolism of DMN, is also planned. Different mouse strains vary in their responsiveness to inducers of aryl hydrocarbon metabolism. Benzo[a]pyrene was administered intrarectally to ICR/Ha mice, which are moderately inducible, and C57BL/6, whose induction response is twofold that of the ICR mice. The noncarcinogenic inducer beta-naphthoflavone or oil was given 24 hours prior to the BP. Although no colon tumors resulted, neoplasms of the lung, forestomach, mammary gland, and lymphoid tissue were seen, and all were reduced significantly in incidence by prior treatment with beta-NF. The protective effect was greater by a factor of 2 in the C57Bl/6 mice, compared to the ICRs. A further investigation is planned involving 6 mouse strains of varying inducibility and per os administration of the carcinogen, to confirm the generally of this finding.